David M. Hume

Biopsies of renal transplants taken within one hour after completion of vascular anastomoses revealed, in seven of 132 cases, the accumulation of large numbers of polymorphonuclear leukocytes within glomerular and peritubular capillaries, with eventual transplant failure in all cases. Serologic studies in all recipients demonstrated pre-existing antibodies reacting with human histocompatibility antigens. Heat eluates from three of four rejected kidneys also contained activity against human histocompatibility antigens. These findings suggest that serum antibody reacted with and became fixed to the histocompatibility antigens of the graft, thereby initiating an acute vascular reaction with early polymorphonuclear-leukocyte margination and progression to widespread capillary thrombosis.

A total of 231 serum samples from 41 patients before and after first and second kidney transplants were investigated for the presence of cytotoxic antibodies. After transplantation 11 of 29 patients had cytotoxic antibodies in contrast to 4 of 21 patients before transplantation. In 10 patients who had their renal grafts removed because of rejection, 9 had demonstrable cytotoxic antibodies. Patients with cytotoxins generally tended to have worse kidney function and transplant failure than patients without cytotoxins (P < 0.005). Moreover, 11 of 14 transplants done in patients with preformed cytotoxins resulted in early transplant failure. From these findings, it appears that humoral cytotoxic antibodies are associated with kidney transplant rejections and that they either act directly on the transplant or serve as indicators of a state of presensitization.

Two patients with copper deficiency had extensive bowel surgery and received long-term parenteral hyperalimentation. One was neutropenic and anemic, with dimorphous erythrocytes. Marrow examination showed a predominance of early granulocytes and cytoplasmic vacuolization of erythroid and myeloid elements. Erythroid development was megaloblastoid and diminished, with increased sideroblasts. These abnormalities disappeared after oral copper therapy, reappeared when therapy was withdrawn, and again disappeared with intravenous copper therapy. The other patient, not as severely hypocupremic, was neutropenic but not anemic. Her marrow showed normoblastic erythropoiesis with cytoplasmic vacuolization of erythroid and myeloid precursors and a predominance of early granulocytes. The neutropenia was corrected with oral copper. Possible mechanisms causing the anemia and neutropenia are discussed. The duodenum seems to be a site of copper absorption. Copper supplementation is needed for patients receiving long-term parenteral hyperalimentation.